The role of sumoylation in retinal progenitor proliferation

• Project/Area Number: 21770246
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: TERADA Koji Osaka Bioscience Institute, 発生生物学部門, 研究員 (70342722)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: Ubc9 / sumo / Xenopus / retina / cell cycle / progenitor / 網膜 / ubc9 / hmgb3 / アフリカツメガエル / 細胞増殖

Research Abstract

Precisely controlled progenitor proliferation is essential for normal development. However, molecular mechanisms, which control the correct timing of cell cycle withdrawal during development, have been poorly understood. We show here that ubc9, a sumo-conjugating enzyme, controls the cell cycle exit of retinal progenitors. We found that ubc9 is highly expressed in retinal progenitors and stem cells in Xenopus embryos. Ubc9 physically and functionally associates with Xenopus hmgb3, which is required for retinal cell proliferation, and prolonged expression of ubc9 and hmgb3 results in suppression of the cell cycle exit of retinal progenitors in a sumoylation-dependent manner. Overexpression of ubc9 and hmgb3 decreased expression of the cell-cycle inhibitor p27^<xic1>. Furthermore, progenitor proliferation is regulated, at least in part, by sumoylation of transcription factor Sp1. These results suggest a significant role of sumoylation for cell cycle regulation in retinal progenitors

Research Products

• [Journal Article] SMOC1 Is Essential for Ocular and Limb Development in Humans and Mice. (2011)
  • Author(s): Okada I., Hamanoue H., Terada K., Tohma T., Megarbane A., Chouery E., Abou-Ghoch J., Jalkh N., Cogulu O., Ozkinay F., Horie K., Takeda J., Furuichi T., Ikegawa S., Nishiyama K., Miyatake S., Nishimura A., Mizuguchi T., Niikawa N., Hirahara F., Kaname T., Yoshiura K., Tsurusaki Y., Doi H., Miyake N., Furukawa T., Matsumoto N., Saitsu H.
  • Journal Title: Am.J.Hum.Genet. 88 Pages: 30-40
  • Peer Reviewed
• [Journal Article] Sumoylation controls retinal progenitor proliferation by repressing cell cycle exit in Xenopus laevis. (2010)
  • Author(s): Terada K., Furukawa T.
  • Journal Title: Developmental Biology 347 Pages: 184-190
  • Peer Reviewed
• [Journal Article] Secreted factor FAM3C (ILEI)is involved in retinal laminar formation. (2010)
  • Author(s): Katahira T., Nakagiri S., Terada K., Furukawa T.
  • Journal Title: Biochem. Biophys. Res.Commun. 392 Pages: 301-306
  • Peer Reviewed
• [Journal Article] Sumoylation controls retinal progenitor proliferation by repressing cell cycle exit in Xenopus laevis. (2010)
  • Author(s): Terada K., Furukawa T.
  • Journal Title: Developmental Biology Volume: 347 Pages: 184-190
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a novel plasma membrane protein, osteoblast inductionfactor (obif), associated with osteoblast differentiation. (2009)
  • Author(s): Kanamoto T., Mizuhashi K., Terada K., Minami T., Yoshikawa H., Furukawa T.
  • Journal Title: BMC Developmental Biology 9 Pages: 70-70
  • Peer Reviewed
• [Presentation] Sumoylation activity of Ubc9 is essential for retinal stem/progenitor cell proliferation (2009)
  • Author(s): 寺田晃士
  • Organizer: The 49th of Annual Meeting of the American Society for Cell Biology(ASCB)
  • Place of Presentation: San Diego Convention Center, San Diego, CA
  • Year and Date: 2009-12-07
• [Presentation] Sumoylation activity of Ubc9, a SUMO-conjugating enzyme, is essential for retinal stem/prosenitor cell proliferation (2009)
  • Author(s): 寺田晃士
  • Organizer: Okinawa Institute of Science and Technology International Workshop, The Retina : Neural Stem Cells and Photoreceptor degeneration
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-10
• [Presentation] SUMO結合酵素Ubc9は網膜幹細胞・未分化前駆細胞の増殖を制御する (2009)
  • Author(s): 寺田晃士
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] Takahisa Furukawa Sumoylation activity of Ubc9 is essential for retinal stem/progenitor cell proliferation (2009)
  • Author(s): Koji Terada
  • Organizer: The 49th of Annual Meeting of the American Society for Cell Biology(ASCB)
  • Place of Presentation: San Diego Convention Center, San Diego, California
• [Presentation] Sumoylation activity of Ubc9, a SUMO-conjugating enzyme, is essential for retinal stem/progenitor cell proliferation Okinawa Institute of Science and Technology International Workshop (2009)
  • Author(s): Koji Terada, Takahisa Furukawa
  • Organizer: The Retina : Neural Stem Cells and Photoreceptor degeneration
  • Place of Presentation: Okinawa, Japan
• [Presentation] SUMO 結合酵素Ubc9 は網膜幹細胞・未分化前駆細胞の増殖を制御する (2009)
  • Author(s): 寺田晃士、古川貴久
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] 網膜幹細胞・未分化前駆細胞の増殖におけるSUMO結合酵素Ubc9の役割 (2009)
  • Author(s): 寺田晃士、古川貴久
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋